PATHOPHYSIOLOGY/FUNCTIONAL SIGNIFICANCE OF WHITE MATTER SIGNAL HYPERINTENSITIES

白质信号高信号的病理生理学/功能意义

• 批准号: 5204967
• 负责人: HELENA C CHUI
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5204967
• 关键词: brain circulation; brain electrical activity; cerebral ischemia /hypoxia; dementia; human old age (65+); human subject; longitudinal human study; magnetic resonance imaging; neural degeneration; neural transmission; neuropsychological tests; positron emission tomography; psychomotor reaction time

The objective of this multi-disciplinary prospective longitudinal study is to elucidate the pathophysiologic and functional significance of white matter signal hyperintensities (WMSH), a highly prevalent funding in brain MRI of normal and demented elderly persons. Evidence for two alternative pathophysiologic models will be examined: 1) WMSH are caused by chronic hypoperfusion of the deep white matter vs. 2) WMSH represent secondary demyelination that results from primary neuronal or axonal loss. A new visual-tactile motor reaction time paradigm has been developed to specifically test a neuroanatomical model for the functional significance of WMSH: namely, that WMSH causes slowing in responses that requires integration of sensory modalities across a distributed network. Four groups of 32 subjects each (n=128) will studied using a longitudinal repeated-measures design. The two major subgroups are comprised of normal elderly persons (CDR 0) and patients with cognitive impairment (CDR 0.5, 1 or 2). Each subgroup is further divided according to the severity of WMSH (mild vs moderate or severe). At baseline, the experimental reaction time paradigm, as well as volumetric studies of WMSH and grey matter will be performed for all subjects. Cerebral blood flow, glucose metabolism in areas of WMSH will be obtained using coregistered position emission tomography (PET) and MRI for a subset of patients with mild or severe WMSH severity. MRI studies, reaction time testing and PET will be repeated after 18 month intervals. Regional quantitative studies of white matter will be performed to test whether the pattern of demyelination corresponds better with the pattern of vascular perfusion or neuronal degeneration. Based upon regional patterns of selective vulnerability, we anticipate that patients with mild so moderate AD, as well as VaD, will be able to perform the visual-tactile motor paradigm. A longitudinal design has been chosen to clarify the temporal relationship between diminished cerebral blood flow and metabolism and to control for individual differences in the experimental variables. Thus, this study is designed to clarify the clinical importance and pathophysiology of WMSH in both AD and VaD.

这项多学科前瞻性纵向研究的目的是 旨在阐明白色的病理生理和功能意义 物质信号高强度（WMSH），一个非常普遍的资金， 正常和痴呆老年人的脑部MRI。证据二 另一种病理生理模型将被检查：1）WMSH是由 深部白色物质慢性低灌注vs. 2）WMSH代表 继发性脱髓鞘，由原发性神经元或轴突 损失一种新的视觉-触觉运动反应时间范式已经被 专门用于测试神经解剖模型的功能 WMSH的意义：即，WMSH导致响应减慢， 需要在分布式网络上集成感觉模态。 将使用纵向研究方法研究4组，每组32例受试者（n = 128）。 重复测量设计。两个主要的亚组由正常的 老年人（CDR 0）和认知障碍患者（CDR 0.5， 1或2）。每个亚组根据以下严重程度进一步划分： WMSH（轻度vs中度或重度）。在基线时，实验反应 时间范例，以及体积研究的WMSH和灰质将 对所有受试者进行。脑血流量、葡萄糖代谢 在WMSH地区，将使用共记录位置发射获得 断层扫描（PET）和MRI用于轻度或重度 WMSH严重性。MRI研究、反应时间测试和PET将被 间隔18个月后重复。白色的区域定量研究 将进行测试是否脱髓鞘的模式， 与血管灌注或神经元灌注的模式更好地对应， 退化 根据选择性脆弱性的区域模式，我们预计 患有轻度或中度AD以及VaD的患者将能够 执行视觉-触觉运动范例。纵向设计已经 选择来阐明大脑功能减退 血液流动和代谢，并控制个体差异， 实验变量。因此，本研究旨在阐明 WMSH在AD和VaD中的临床重要性和病理生理学。